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Diaphyseal Dysplasia
Sunday, 14 August 2005
Sunday, 14 August 2005
Camurati Engelmann Disease, Diaphyseal Sclerosis, Engelmann Disease, Progressive Diaphyseal Dysplasi


Diaphyseal dysplasia is a rare, inherited disorder of bone that is characterized by thickening and symmetric malformation of the shaft of the long bones. These bony changes frequently lead to bone pain, weakness and wasting of muscles, waddling walk, excessive fatigability, and abnormal stature.


Diaphyseal dysplasia is a rare disorder that tends to run in families. There is no known racial or gender predilection. As of 1999, 208 cases of variable severity had been reported in the medical literature. The true incidence is not known.

Signs and Symptoms

Children with diaphyseal dysplasia usually show symptoms by age 10, however there is a lot of variability, and symptoms can occur as early as 20 months or as late as in adulthood. Furthermore, the severity and duration of symptoms can be highly variable. Close to 75% of patients who present in childhood experience the classic symptoms of muscular weakness and wasting on both sides of the body, fatigue, waddling walk, and severe limb pain. The bones most often involved are the femur, tibia, humerus, ulna, radius, and bones of the hands and feet, as well as sometimes the bones at the base of the skull. Over time, the disease may also progress and cause secondary scoliosis (abnormal curvature of the spine) or other disorders of the spine. Muscular weakness occurs because the widening of the long bones weakens the attached muscles, which, if happening in the leg bones of infants, may in turn lead to a delay in walking. The muscle wasting, especially in the legs, leads to an appearance of malnutrition in some patients. In addition to skeletal symptoms, many other findings have also been described. For patients whose skull bones are affected, skull thickening can lead to compression of cranial nerves and ultimately facial paralysis, hearing difficulties, or loss of vision. Likewise, the growth of bone in the space behind the eye causes a condition called exophthalmos, or the bulging of the eyeball, in 50% of cases. Other eye problems that may occur include diploplia (double vision), periorbital edema (swelling around the eye), and ecchymosis (bruising), also all caused by the bone thickening. Children with diaphyseal dysplasia may also suffer from problems of the bone marrow, such as anemia (low red blood cell count), leukopenia (low white blood cell count), hepatosplenomegaly (enlarged liver and spleen), and increased likelihood of recurrent infections. Other symptoms that have been described include: lower leg swelling, spasms of the arteries in the fingers (known as the Raynaud phenomenon), and other nail problems.

Possible Causes

Diaphyseal dysplasia is a genetic disorder that is inherited in an autosomal dominant fashion, meaning that one copy of the abnormal gene is sufficient to cause the disorder. Children who are affected usually have an affected parent because the condition is dominant. The gene responsible for diaphyseal dysplasia (TGFbeta1) is located on chromosome 19 and codes for a growth factor that affects bone development. There have been many different mutations in the TGFBeta1 gene that have all been linked to diaphyseal dysplasia, and although the disease is classified as autosomal dominant in inheritance, some people with the mutation will show no abnormalities—leading to so-called “skipped generations” within a family. Diaphyseal dysplasia is believed to be caused by the abnormal production of bone growth factors that, throughout life, control the constant formation, breakdown, and rebuilding of bone. In the case of diaphyseal dysplasia, the balance between the processes of forming and breaking down bone is likely shifted towards increased bone tissue production.


The diagnosis of diaphyseal dysplasia is usually made by imaging tests, using x-ray, MRI (magnetic resonance imaging), and/or bone scintigraphy, a scan that measures the activity of bone. X-ray and MRI may show symmetric thickening of long bones at the center of the shaft, usually first in the leg bones before spreading elsewhere. In patients with cranial involvement, thickening also appears on skull images, along with decreased size of the holes found in normal skulls. On scintigraphy, patients with diaphyseal dysplasia will show hyperactivity of bone formation. Despite the muscular changes associated with diaphyseal dysplasia, a muscle biopsy would show no significant abnormalities, and would likely be used only to rule out a primary muscle disorder. The diagnosis can be confirmed by blood tests looking for abnormalities of the TGFbeta1 gene.


While there is no specific cure for diaphyseal dysplasia, treatment should be focused on supportive care to treat the related symptoms. One class of medication commonly used is the corticosteroids, which have been found to not only relieve pain symptoms, but also help control the ongoing abnormal formation of bone. Potential side effects of steroids include weight gain, mood changes, and osteoporosis. Additional pain-killers can be used on an as needed basis. Surgery may be indicated for patients for whom the excess bone growth has led to intolerable symptoms—for example, surgical removal of bone compressing the eyeball.


In most cases, resolution of symptoms occurs on its own by age 30, although the patient still retains the existing structural deformities. Overall, the prognosis for those with diaphyseal dysplasia is fairly good, if not unpredictable, with many patients living normal, symptom-free lives.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.


National Institute of Arthritis and Musculoskeletal and Skin Diseases
Information and links to ongoing research and clinical trials on various musculoskeletal and skin diseases.

Genetic Alliance: Advocacy, Education & Empowerment
General resources, glossary, and tools for understanding genetic disease.

WebMD Health
Nice general synopsis on the condition.

Pediatric Bone Disorders
Concise summary of the major pediatric bone disorders.

Little People of America
Very credible website and group devoted to improving the lives of little people.

Short Persons Support
Lots of useful links to consider.


Google Search for Diaphyseal Dysplasia

References and Sources

Online Mendelian Inheritance in Man. (2004). #131300 Camurati-Englemann Disease. Janssens K, et al. (2000). Localisation of the gene causing diaphyseal dysplasia Camurati-Engelmann to chromosome 19q13, J Med Genet, 37, p 245-49. Choudhury P, et al. (2000). Engelmann’s Disease with Cardiomyopathy, Indian Pediatrics, 37, p 1373-76. Y Naveh, et al. (1984). Progressive diaphyseal dysplasia: genetics and clinical and radiologic manifestations, Pediatrics, 74:3, p 399-405.